Benzimidazole derivatives as antihistamine agents

Abstract

The invention relates to compounds of formula (I), or a pharmaceutically acceptable salt or solvate thereof, a method of synthesis of said compounds, pharmaceutical compositions comprising them and their use in the treatment and/or prevention of conditions mediated by H 1 histamine receptor, such as allergic disorders or diseases.

The invention claimed is: 
     
       1. A compound of formula (I): 
       
         
           
           
               
               
           
         
         wherein: 
         R 1  is an optionally substituted C 1 -C 6  alkyl group; 
         R 2  is selected from hydrogen, —COR b , —COOR c  and C 1 -C 6  alkyl optionally substituted with —OR d , or —COOR e , wherein R b , R c , R d  and R e  are independently selected from hydrogen and C 1 -C 6  alkyl; 
         n is 1, 2 or 3; 
         X is CH or N; 
         or a pharmaceutically acceptable salt or solvate thereof. 
       
     
     
       2. The compound according to  claim 1 , wherein X is CH. 
     
     
       3. The compound according to  claim 1 , wherein R 1  is a C 1 -C 6  alkyl group optionally substituted with C 1 -C 6  alkyl, C 3 -C 7  cycloalkyl, 3- to 10-membered heterocyclyl, C 6 -C 12  aryl, 3- to 10-membered heteroaryl, halogen, CN, NO 2 , NH 2 , NH(C 1 -C 6  alkyl), N(C 1 -C 6  alkyl) 2 , or —OR a , wherein R a  is selected from hydrogen, C 1 -C 6  alkyl, halo(C 1 -C 6  alkyl), C 3 -C 7  cycloalkyl, 3- to 10-membered heterocyclyl, C 6 -C 12  aryl, (C 6 -C 12 )aryl(C 1 -C 6 )alkyl, and 3- to 10-membered heteroaryl. 
     
     
       4. The compound according to  claim 1 , wherein R 1  is a C 1 -C 6  alkyl group optionally substituted with 3- to 10-membered heteroaryl or —OR a , wherein R a  is selected from hydrogen, C 1 -C 6  alkyl, C 6 -C 12  aryl, (C 6 -C 12 )aryl(C 1 -C 6 )alkyl, and 3- to 10-membered heteroaryl. 
     
     
       5. The compound according to  claim 1 , wherein R 1  is a C 1 -C 6  alkyl group optionally substituted with 5- to 6-membered heteroaryl or —OR a , wherein R a  is selected from C 1 -C 6  alkyl, phenyl, and 5- to 6-membered heteroaryl. 
     
     
       6. The compound according to  claim 1 , wherein R 1  is a C 1 -C 6  alkyl group substituted with —OC 1 -C 6  alkyl. 
     
     
       7. The compound according to  claim 1  which is selected from the following compounds: 
       
         
           
           
               
               
           
         
         
           
           
               
               
           
         
         or a pharmaceutically acceptable salt or solvate thereof. 
       
     
     
       8. A pharmaceutical composition comprising a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt or solvate thereof, and at least one pharmaceutically acceptable excipient. 
     
     
       9. A method of treatment of an allergic disorder or disease, which method comprises administering to a patient in need of such a treatment a therapeutically effective amount of a compound of formula (I) as defined in  claim 1  or a pharmaceutically acceptable salt or solvate thereof, wherein the allergic disorder or disease is selected from rhinitis, conjunctivitis, rhinoconjunctivitis, dermatitis, urticaria and asthma.